TABLE 1.
Genetic Findings in Patients Categorized by Clinical Phenotype
| Demographics |
Genetic Variants |
||||||
|---|---|---|---|---|---|---|---|
| Family | Patient # | Status | Family History | Gene | Nucleotide | Amino Acid | Classification ACMG 2015 |
| ARVC | |||||||
| A | 1 | P | Yes | PKP2 | c.1755_1756insTTGACTCA | L586fsX658 | Pathogenic |
| B | 1 | P | Yes | PKP2 | c.2203C>T | R735X | Pathogenic |
| C | 1 | P | Yes | PKP2 | c.1821dupT | V608CfsX6 | Pathogenic |
| C | 2 | FM | Yes | PKP2 | c.1821dupT | V608CfsX6 | Pathogenic |
| D | 1 | FM | Yes | PKP2 | c.1613G>A | W538X | Pathogenic |
| E | 1 | P | No | ||||
| F | 1 | FM | Yes | PKP2 | c.1511–1 G>A | Likely pathogenic | |
| PKP2 | c.976 G>A | A326T | VUS | ||||
| G | 1 | P | Yes | PKP2 | c.2489+1 G>A | Pathogenic | |
| DSC2 | c.1028_1030deLTTA | ILe343deL | VUS | ||||
| H | 1 | P | Yes | PKP2 | c.2062T>C | S688P | VUS |
| H | 2 | FM | Yes | Not tested | |||
| I | 1 | P | Yes | PKP2 | c.1237C>T | R413X | Pathogenic |
| J | 1 | P | Yes | PKP2 | c.1237C>T | R413X | Pathogenic |
| DSC2 | c.996T>G | Y332X | Likely pathogenic | ||||
| K | 1 | P | Yes | PKP2 | c.951deLG | H318TfsX2 | Likely pathogenic |
| L | 1 | P | Yes | PKP2 | c.1237C>T | R413X | Pathogenic |
| M | 1 | P | No | ||||
| N | 1 | FM | Yes | PKP2 | c.2489+1 G>A | Pathogenic | |
| LD ACM | |||||||
| O | 1 | P | Yes | DSP | c.3526deLG | V1176fsX20 | Likely pathogenic |
| DSG2 | c.1003A>G | T355A | VUS | ||||
| P | 1 | FM | Yes | Not tested | |||
| Q | 1 | P | No | DSP | c.2920deLA | T974fsX3 | Likely pathogenic |
| R | 1 | FM | Yes | LMNA | c.1621 C>T | R541C | Likely pathogenic |
| R | 2 | FM | Yes | LMNA | c.1621 C>T | R541C | Likely pathogenic |
| S | 1 | FM | Yes | LMNA | c.637C>T | R225X | Pathogenic |
| T | 1 | P | Yes | DSP | c.3434deLC | A1145fsX14 | Likely pathogenic |
| BiV ACM | |||||||
| U | 1 | P | Yes | DSP | c.1873C>T | Q625X | Likely pathogenic |
| DSP | c.6442G>A | A2148T | VUS | ||||
| V | 1 | P | Yes | DSG | c.152G>T | W51L* | VUS |
| V | 2 | FM | Yes | DSG2 | c.152G>T | W51L* | VUS |
| W | 1 | P | Yes | PKP2 | c.2509deLA | S837VfsX94* | Pathogenic |
| X | 1 | P | No | PKP2 | c.1034+1 G>T | Pathogenic | |
| Y | 1 | P | No | DSP | c.478C>T | R160X | Pathogenic |
| DSP | c.8020G>A | A2647T | |||||
| Z | 1 | P | Yes | DSC2 | c.631–2 A>G | Pathogenic | |
| AA | 1 | P | Yes | PKP2 | c.1162C>T | R388W | VUS |
| PKP2 | c.2301deLC | G769LfsX31 | Likely pathogenic | ||||
| BB | 1 | P | No | DES | c.347A>G | N116S | Likely pathogenic |
| Unaffected family members | |||||||
| CC | 1 | FM | Yes | DSP | c.3474_3475insA | G1159RfsX3 | Pathogenic |
| DD | 1 | FM | Yes | DSP | c.478C>T | R160X | Pathogenic |
| DD | 2 | FM | Yes | DSP | c.478C>T | R160X | Pathogenic |
| EE | 1 | FM | Yes | PKP2 | c.1211_1212insT | V406SfsX4 | Pathogenic |
| EE | 2 | FM | Yes | PKP2 | c.1211_1212insT | V406SfsX4 | Pathogenic |
| FF | 1 | FM | Yes | PKP2 | c.2146–1 G>C | Pathogenic | |
| GG | 1 | FM | Yes | DES | c.735 +1G>A | Likely pathogenic | |
| HH | 1 | FM | Yes | TMEM43 | c.1073C>T | S358L | Pathogenic |
| W | 2 | FM | Yes | PKP2 | c.2509deLA | S837VfsX94 | Pathogenic |
| W | 3 | FM | Yes | PKP2 | c.2509deLA | S837VfsX94 | Pathogenic |
| U | 2 | FM | Yes | DSP | c.1873C>T | Q625X | Likely pathogenic |
| II | 2 | FM | Yes | LMNA | c.961C>T | R321X | Pathogenic |
| LMNA | c.992G>A | R331G | VUS | ||||
| JJ | 1 | FM | Yes | LMNA | c.1621 C>T | R541C | Likely pathogenic |
| J | 2 | FM | Yes | DSC2 | c.996T>G | Y332X | Likely pathogenic |
| C | 3 | FM | Yes | PKP2 | c.1821dupT | V608CfsX6 | Pathogenic |
*
Homozygous.
ACM = arrhythmogenic cardiomyopathy; ACMG = American College of Medical Genetics and Genomics; ARVC = arrhythmogenic right ventricular cardiomyopathy; BiV = biventricular; DES =desmin; DSC2 =desmocollin-2; DSP =desmoplakin; FM = family member; LD = left dominant; LMNA =lamin A/C; P = proband; PKP2 =plakophilin-2; TMEM43 =transmembrane protein 43; VUS = variant of unknown significance.